Our understanding of the neural actions of prolactin (PRL) and its biochemical basis has expanded greatly over the past three decades. During this time, major progress has been made that includes the elucidation of how PRL accesses the brain, identification of the PRL receptor and the sites where it is expressed within the brain, determination of the neurochemical mechanism of action of PRL and its effect on genomic expression in neurons, identification of the neural sites where PRL acts to stimulate maternal behavior and related affective states, and exploration of how life experiences impact neural PRL receptor activity and actions...

The "hunger" hormone, ghrelin, is powerfully orexigenic. Even in the absence of hunger, ghrelin delivery to rats increases consumption of chow as well as palatable foods and increases motivated behaviour for palatable food rewards. Inspired by the finding that ghrelin increases the selection of chow in rats offered a choice diet (lard, sucrose or chow) and even in rats bingeing on a high fat diet, we sought to explore whether ghrelin's effects on motivation extend to regular chow. Rats were conditioned to lever press for either chow or sucrose pellets in a progressive ratio (PR) operant conditioning task...

Although RFamide-related peptide (RFRP) preproprotein sequence is known in mice, until now the molecular structure of the mature, functional peptides processed from the target precursor molecule has not been determined. In the present study we purified endogenous RFRP1 and RFRP3 peptides from mouse hypothalamic tissue extracts using immunoaffinity column conjugated with specific antibodies against the mouse C-terminus of RFRP-1 and RFRP-3. Employing liquid chromatography coupled with mass spectrometry (LC-MS) we demonstrated, that RFRP1 consists of 15 and RFRP3 of 10 amino acid residues (ANKVPHSAANLPLRF-NH2 and SHFPSLPQRF-NH2 , respectively)...

To understand the contribution of intrinsic membrane properties to the different firing patterns of oxytocin (OT) and vasopressin (VP) neurons in vivo, in vitro studies are needed, where stable intracellular recordings can be made. Combining immunochemistry for OT and VP and intracellular dye injections allows characterization of identified OT and VP neurons, and several differences between the two cell types have emerged. These include a greater transient K+ current that delays spiking to stimulus onset, and a higher Na+ current density leading to greater spike amplitude and a more stable spike threshold, in VP neurons...

Sulfated cholecystokinin octapeptide (CCK-8s) is involved in feeding regulation as an anorexigenic neuropeptide in vertebrates. In rodents, intracerebroventricular (ICV) administration of CCK-8s has been shown to affect not only feeding behavior, but also psychomotor activity. However, there is still no information regarding the psychophysiological effects of CCK-8s in goldfish. Therefore, we examined the effect of synthetic goldfish (gf) CCK-8s on psychomotor activity in this species. ICV administration of gfCCK-8s at 0...

Obesity and type 2 diabetes are a veritable global pandemic. There is an imperative to develop new therapies for these conditions that can be delivered at scale to patients, which deliver effective and titratable weight loss, amelioration of diabetes, prevention of diabetic complications and improvements in cardiovascular health. Although agents based on glucagon-like peptide-1 (GLP-1) are now in routine use for diabetes and obesity, the limited efficacy of such drugs means that newer agents are required. By combining the effects of GLP-1 with other gut and metabolic hormones such as glucagon (GCG), oxyntomodulin, glucose-dependent insulinotropic peptide (GIP) and peptide YY, we may obtain improved weight loss, increased energy expenditure and improved metabolic profiles...

Ghrelin is a gastric hormone that has been implicated in the neurobiology of alcohol drinking. We have recently developed a ghrelin receptor (GHSR) knockout (KO) rat model, which exhibits reduced food consumption and body weight. In addition, recent preliminary work suggests that the gut-microbiome, which appears to interact with the ghrelin system, may modulate alcohol drinking. Here, we investigated the effects of GHSR deletion on alcohol consumption utilizing GHSR KO and wild type (WT) rats in three separate alcohol consumption paradigms: 1...

In the rat supraoptic nucleus, every oxytocin cell projects to the posterior pituitary, and is involved in both reflex milk ejection during lactation, and in regulating uterine contractions during parturition. All are also osmosensitive, regulating natriuresis. All are also regulated by signals that control appetite, including neural and hormonal signals that arise from the gut after food intake and from the sites of energy storage. All are also involved in sexual behaviour, anxiety-related behaviours, and social behaviours...

INTRODUCTION: Middle age has been linked with various dysfunctional eating patterns in women. The hormone ghrelin is related to food intake, with plasma levels rising before eating and decreasing immediately afterwards. Animal research has shown that estradiol is an antagonist of ghrelin. Given that both menopause and anorexia nervosa (AN) are states characterised by reduced estradiol, the goal of the present study was to investigate for the first time whether menopausal status and a history of AN are linked with altered ghrelin levels in middle-aged women...

A population of kisspeptin neurons located in the hypothalamic arcuate nucleus (ARN) very likely represent the gonadotrophin-releasing hormone pulse generator responsible for driving pulsatile luteinizing hormone secretion in mammals. As such, it has become important to understand the neural inputs that modulate the activity of ARN kisspeptin (ARNKISS ) neurons. Using a transgenic GCaMP6 mouse model allowing the intracellular calcium levels (i[Ca2+ ]) of individual ARNKISS neurons to be assessed simultaneously, we examined whether the circadian neuropeptides vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP) modulated the activity of ARNKISS neurons directly...

Congenital Hypogonadotropic Hypogonadism (CHH) is a challenging inherited endocrine disorder characterized by absent or incomplete pubertal development and infertility due to low action/secretion of the hypothalamic gonadotrophin-releasing hormone (GnRH). Given a growing list of gene mutations accounting for CHH, application of massively parallel sequencing has become an excellent molecular diagnosis approach since it has enabled simultaneous evaluation of many genes. The study proposes the use of Whole Exome Sequencing (WES) to identify causative and modifying mutations based on a phenotype-genotype CHH analysis by in-house exome pipeline...

Metabolic health founds on a homeostatic balance which has to integrate the daily changes of rest/activity and feeding/fasting cycles. A network of endogenous 24-hour circadian clocks helps to anticipate daily recurring events and adjust physiology and behavioral functions accordingly. Circadian clocks are self-sustained cellular oscillators based on a set of clock genes/proteins organized in interlocked transcriptional-translational feedback loops. The body's clocks need to be regularly reset and synchronized with each other to achieve coherent rhythmic output signals...

Gonadotropin releasing hormone (GnRH) neurone function is dependent upon gonadal steroid hormone feedback, which is communicated in large part through an afferent neuronal network. The classical neurotransmitters gamma-aminobutyric acid (GABA) and glutamate are important regulators of GnRH neurone activity and are implicated in mediating feedback signals. We aimed here to determine whether GABAergic or glutamatergic input to GnRH neurones differs between males and females and/or exhibits morphological plasticity in response to steroid hormone feedback in females...

Orexigenic peptide ghrelin and its receptor have been extensively investigated as potential therapeutic targets, primarily due to their role in feeding initiation and growth hormone (GH) release. However, no specific ghrelin targeting anti-obesity or cachexia therapeutics are available for clinical use thus far and further efforts in this direction are warranted. Our objective was to find new peptide drug leads modulating ghrelin signal transduction. By targeting neutralizing antibodies against ghrelin with phage display libraries we aimed to identify peptides binding to the cognate receptor...

The subfornical organ (SFO) lacks the normal blood brain barrier and senses the concentrations of many different circulating signals including glucose and angiotensin II (ANG II). ANG II has recently been implicated in the control of food intake and body weight gain. The present study assessed whether single SFO neurons sense changes in glucose and ANG II, and if changes in glucose concentration alters these neurons responsiveness to ANG II. SFO neurons dissociated from male Sprague-Dawley rats (100-175g) were used...

Since the 1950's (1) the systems level interactions between the hypothalamus, pituitary and end organs such as the adrenal, thyroid and gonads have been well known, however it is only over the last three decades that advances in molecular biology and information technology have provided a tremendous expansion of knowledge at the molecular level. This article is protected by copyright. All rights reserved.

Apart from the primary metabolic symptoms of obesity and/or diabetes, there are numerous secondary problems, including disruptions of the reproductive system. The KNDy neurones, which express kisspeptin, neurokinin B and dynorphin A and are located in the arcuate nucleus of the hypothalamus (ARC), are important regulators of reproduction. Their functions are highly influenced by metabolic and hormonal status. We have previously shown that, in male rats with experimentally-induced diabetes type 2 (but not with high-fat diet-induced obesity), there are alterations in the number of these cells...

Sex differences are a prominent feature of the pathophysiology of psychiatric disorders, such as major depressive disorder, which affects women at a higher incidence than men. Research suggests that the most potent endogenous oestrogen, 17β-oestradiol, may have therapeutic potential in treating depression. However, preclinical studies have produced mixed results, likely as a result of various methodological factors such as treatment duration. The present study aimed to investigate the effects of ovariectomy and chronic 17β-oestradiol treatment via a s...

Methods used to study neuroendocrinology have been as diverse as the discoveries to come out of the field. Maintaining live neurons outside of a body in vitro was important from the beginning, building on methods that dated back to at least the first decade of the 20th century. Neurosecretion defines an essential foundation of neuroendocrinology based on work that began in the 1920's and 1930's. Throughout the first half of the 20th century, many paradigms arose for studying everything from single neurons to whole organs in vitro...